Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the preceding paper, we have identified a protein of Mr = 118,000 which is induced by stress conditions that lead to cessation of DNA synthesis and cell division (Verma, R., Iida, H., and Pardee, A.B. (1988) J. Biol. Chem. 263, 8569-8575). In the current study, we have investigated the possible role this protein may play in cellular proliferation by studying p118 expression in mutants of the cAMP metabolic pathway. The cyr 1-2 mutant gene encodes a thermolabile adenylate cyclase whose activity is only 7% of wild type even at permissive temperatures (23 degrees C). We have found that at 23 degrees C, the G1 period was 5-fold longer in cyr 1-2 than in CYR1+ cells and that p118 was constitutively expressed in these slow cycling mutants. Addition of 8-bromo-cAMP to cyr 1-2 mutants restored growth at both the restrictive and permissive temperatures and resulted in a shut-off in the synthesis of p118. The effect of the analog on p118 expression was rapid, preceding the increase in cell number and percentage-budded cells. In contrast to wild type cells, p118 synthesis was not induced by sulfur starvation in RAS2val19 mutants possessing high levels of adenylate cyclase activity and bcy1 mutants defective in the regulatory subunit of cAMP-dependent protein kinase. A large body of evidence exists supporting a role of cAMP in positive control of cell proliferation. It is therefore possible that conditions which decrease cAMP arrest growth through a chain of events that include p118 induction.
 ...
PMID:Modulation of expression of the stress-inducible p118 of Saccharomyces cerevisiae by cAMP. II. A study of p118 expression in mutants of the cAMP cascade. 283 58

We have described in D. discoideum a highly organized cell aggregation that is mediated by cAMP. After suitable differentiation induced by starvation, the cells develop the capacity to orient in gradients of cAMP and to secrete cAMP in response to cAMP. This signaling response sets up the cell-cell relay of cAMP waves that transiently orients the cells toward the center. Both the signaling response and the chemotactic response, measured in isolated cells, adapt. The kinetics and properties of adaptation of the two responses are similar and may be due to the same mechanism. The mechanism does not involve protein synthesis, a change in the number or affinity of surface receptors, or the activation of adenylate cyclase. Adaptation of signaling is essential for the oscillatory production of cAMP at the aggregation centers and ensures that the cAMP waves move steadily toward the edge of the aggregation territories. Adaptation of the chemotactic response also ensures that cells do not reorient away from the center in the gradient presented by the trailing edge of the wave. We have demonstrated that both chemotaxis and cAMP signaling are mediated by the same surface receptor. The polypeptide containing the binding site of the receptor has been identified by photoaffinity labeling with [32P]-8-N3-cAMP as a diffuse band of 41,000-45,000 Mr. The receptor and adenylate cyclase copurify on a homogeneous class of vesicles resistant to extraction by nonionic detergents. A GTP-binding protein that is a substrate for cholera toxin-catalyzed ADP ribosylation is found in supernatants and membranes and may be similar to the Gs regulatory protein of adenylate cyclase in higher organisms. The mechanism of activation of the adenylate cyclase and chemotactic machinery is unknown. We have been able to inhibit the activation of the adenylate cyclase selectively and rapidly with agents acting to crosslink cell surface components, which may give a clue to the activation mechanism. The elaborate mechanisms of cell-cell communication occurring in D. discoideum are without precedent in biological literature, although models of oscillatory wave propagation have been proposed to account for pattern formation. Although it is unlikely that extracellular cAMP would be involved, it is not inconceivable that such mechanisms occur during the development of more evolutionarily advanced organisms. The organized communication system in D. discoideum is only apparent when cells are plated uniformly on a flat surface; such organized movements occurring in a three-dimensional structure such as an embryo would be very difficult to discern.
 ...
PMID:Cell-cell interactions in the development of Dictyostelium. 285 27

We undertook a study to define the role of cyclic AMP [cAMP] in modulating the secretion of transcobalamin II (TC-II) in the mouse macrophage like cell line J774. J774 was observed to secrete large amounts of TC-II, particularly in the presence of 8-bromo cAMP or cholera toxin or when grown in medium supplemented with low concentrations of horse serum (1% or 5%) or in serum-free medium. Variant cell lines derived from J774 and deficient either in adenylate cyclase (ac -) or cAMP-dependent protein kinase (pk -) activity showed very low and intermediate levels of basal secretory activity of TC-II, respectively, compared to J774. Maximum secretory activity of TC-II was observed in J774 under conditions in which growth was poorest (in the presence of 8-bromo-cAMP or 1% or 5% horse serum-supplemented medium or in serum-free medium). Cells grown in serum-free medium were found to have elevated basal adenylate cyclase activity and cAMP levels compared to those grown in medium supplemented with 20% horse serum. The data from this study demonstrate a negative correlation between growth activity and TC-II secretion in the J774 cell line. The stimulatory effect of exogenous cAMP on TC-II secretion by J774, the reduced secretory activity of the variant lines ac- and pk- and the observed increase in cell cAMP levels under conditions of serum starvation in which TC-II secretion is considerably enhanced, suggest that cell cAMP is an important modulator of TC-II secretion and growth behavior in the J774 cell line.
 ...
PMID:The modulation of transcobalamin II (TC-II) production by cyclic adenosine 3',5'-monophosphate in the murine macrophage cell line J774: relationship to growth behavior. 300 44

A gene, PDE2, has been cloned from the yeast Saccharomyces cerevisiae that, when present in high copy, reverses the phenotypic effects of RAS2Val19, a mutant form of the RAS2 gene that renders yeast cells sensitive to heat shock and starvation. It has previously been shown that the RAS proteins are potent activators of yeast adenylate cyclase. We report here that PDE2 encodes a high-affinity cAMP phosphodiesterase that shares sequence homology with animal cell phosphodiesterases. These results therefore imply that the effects of RAS2Val19 are mediated through its changes in cAMP concentration.
 ...
PMID:Cloning and characterization of the high-affinity cAMP phosphodiesterase of Saccharomyces cerevisiae. 302 32

The Saccharomyces cerevisiae gene YPT1 encodes a protein that exhibits significant homology to the mammalian ras proteins. Using gene disruption techniques, we have shown that the intact YPT1 gene is required for spore viability. Lethality caused by loss of YPT1 function, unlike that caused by loss of the yeast ras homologs RAS1 and RAS2 function, is not suppressed by the bcy1 mutation, suggesting that YPT1 does not act through the adenylate cyclase regulatory system. A cold-sensitive allele, ypt1-1, was constructed. At the nonpermissive temperature, mutants died, exhibiting aberrant nuclear morphology, as well as abnormal distribution of actin and tubulin. The mutant cells died without exhibiting classical cell-cycle-specific arrest; nevertheless, examination of cellular DNA content suggests that the YPT1 function is required, particularly after S phase. Cells carrying the ypt1-1 mutation died upon nitrogen starvation even at a temperature permissive for growth; diploid cells homozygous for ypt1-1 did not sporulate. The YPT1 gene is thus involved in nutritional regulation of the cell cycle as well as in normal progression through the mitotic cell cycle.
 ...
PMID:The ras-like yeast YPT1 gene is itself essential for growth, sporulation, and starvation response. 330 75

Various truncated CYR1 genes of Saccharomyces cerevisiae were fused to efficient promoters and expressed in Escherichia coli and S. cerevisiae cells with or without the RAS genes. The catalytic domain of adenylate cyclase encoded by the 3'-terminal 1.3 kb region of the open reading frame of the CYR1 gene produced cyclic AMP, irrespective of the presence of RAS genes. The product of the 3'-terminal 2.1 kb region of CYR1 showed guanine nucleotide-dependent adenylate cyclase activity and produced a large amount of cAMP in the presence of the RAS gene. Thus, the domain encoded by the 0.8 kb region adjacent to the catalytic domain is associated with the regulatory function of the RAS products. The cyr1 RAS1 RAS2 cells carrying the 3'-terminal 1.3 kb region of CYR1 were unable to respond to environmental signals such as sulfur starvation and temperature shift, but the cyr1 cells carrying the 2.1 kb region and at least one RAS gene were able to respond to these signals. The environmental signals may be transferred to the adenylate cyclase system through the RAS products.
 ...
PMID:Identification of the domain of Saccharomyces cerevisiae adenylate cyclase associated with the regulatory function of RAS products. 332 73

Adenylate cyclase of aggregation phase Dictyostelium discoideum is activated by extracellular adenosine 3', 5'-cyclic monophosphate (cAMP), and the cAMP synthesized is secreted. The distribution of the enzyme was determined in sucrose gradients loaded with whole cell lysates. Cell lysates prepared after 4.5 hr of starvation revealed membranes containing adenylate cyclase at 44% and 33% sucrose. The activity of the latter peak was detected in the presence of the detergent (CHAPS), 3-(3-cholamidopropyl) dimethylammonio-3-propanesulfonate, which inhibited the activity of the former to some extent. Adenylate cyclase activity of the 2 peaks differed with respect to solubility in CHAPS and their kinetics. The 44% sucrose region of the gradient contained the bulk of the plasma membranes, as judged by a cell surface glycoprotein marker (contact site A). The 33% peak is composed of small vesicular structures, as determined by electron microscopy. The distribution of adenylate cyclase activity detected in sucrose gradients shifted from the 33% to the 44% sucrose peak during development. In addition, the 44% peak became increasingly resistant to the inhibitory effect of CHAPS. Both changes were accelerated by extracellular cAMP, but only the latter was abolished when the production of endogenous cAMP was inhibited by caffeine. Pulsing cells with cAMP overcame the inhibitory effect of caffeine.
 ...
PMID:Developmentally regulated compartmentalization of adenylate cyclase in Dictyostelium discoideum. 341 88

Pertussis toxin is now used as an experimental tool for the study of receptor-mediated inhibitory systems. Based on our previous work, where we demonstrated in rats pretreated with pertussis toxin the blockade of negative chronotropic and reduction of negative inotropic effects of carbamoylcholine, we examined the effects of cholinergic agents on the rat heart adenylate cyclase activity. Pertussis toxin pretreatment reduced the inhibitory effects of cholinergic agents on adenylate cyclase activity only very slightly. This contrasts to the strong antagonistic effect on the phenylisopropyladenosine-induced inhibition of adrenergic lipolysis, including that increased lipolysis after 48 hours starvation. These data suggest that the strong inhibition of negative chronotropic effect of muscarinic drugs by pertussis toxin may be related to the recently described No protein rather then Ni protein from the adenylate cyclase complex.
 ...
PMID:The action of pertussis toxin on heart adenylate cyclase and lipolysis in the parametrial adipose tissue of the rat. 343 5

In the first few hours after starvation, the developing cAMP secretory system in Dictyostelium discoideum has been observed to be successively in one of four states: (a) quiescent, (b) excitable (capable of relay), (c) autonomously oscillating, and (d) secreting at a high steady level. A theoretical model is presented which demonstrates that the proximal cause of the transitions between different types of behavior may be slow changes in the activities of the enzymes adenylate cyclase and phosphodiesterase. These changes affect the stability properties of the steady state admitted by the cAMP signalling system. Sustained oscillations develop when the steady state is unstable, whereas relay of cAMP signals occurs upon perturbation of a stable steady state for parameter values close to those which produce oscillations. The developmental path suggested in the adenylate cyclase-phosphodiesterase space for the sequential transitions compares with the time course observed for the synthesis of these enzymes after starvation. It is suggested that there is general significance for the understanding of differentiation in the example given of a state-point following a developmental path in parameter space, moving from one behavioral domain to another, and thereby bringing about shifts in qualitative behavior.
 ...
PMID:Control of developmental transitions in the cyclic AMP signalling system of Dictyostelium discoideum. 625 48

Young swine (28 days of age) were fed an isocaloric and isonitrogenous diet with either a high fat or a low fat content for 3 to 4 weeks. The adipose tissue lipolytic rate was higher in the group fed the high fat diet. However, there was no effect of diet on the activities of several of the enzymes controlling the lipolytic process, i.e., adenylate cyclase, phosphodiesterase and hormone-sensitive lipase. No effect of diet on the activity of lipoprotein lipase was detected. Fasting for 72 hr, but not for 24 or 48 hr, caused an increase in the lipolytic rate. There was also a decrease in cell size after a 72-hr fast (P greater than .05) such that the increased rate was not significant when the data were expressed on a cell basis. Inexplicable transient changes in adenylate cyclase activity, as well as a decrease in the activity of the low affinity phosphodiesterase (doubtful physiological significance), were detected during starvation. Starvation depressed the adipose tissue lipoprotein lipase activity but had no effect on the hormone-sensitive lipase activity.
 ...
PMID:Effect of nutritional status on swine adipose tissue lipolytic activities. 627 20


<< Previous 1 2 3 4 5 6 7 Next >>